Phenethylamines can be depicted as:
and the 2C-X compounds are substituted 2,5-dimethoxyphenethylamines in which R3 and R6 are methoxy, and RN, Rα and Rβ are each hydrogen.
The ‘NBOMe’ compounds are highly potent hallucinogenic phenethylamine derivatives which have recently been encountered in cases of recreational drug use. Specifically they are 2C-X compounds in which RN is an optionally substituted benzyl derivative—also known as N-benzyl derivatives of the substituted 2,5-dimethoxyphenethylamine 2C-X compounds. This modification appears to significantly enhance their potency and therefore increases the risk of overdoses by miscalculation of dose. For example, while a dose of 2C-I is around 20 milligrams, the dose of the NBOMe equivalent (25I-NBOMe) is less than one milligram (Blaazer et al. 2008). NBOMe compounds act as potent serotonin agonists particularly at the 5-HT2A receptors which mediate the primary effects of hallucinogenic drugs. Their effects have been compared to lysergic acid diethylamide (LSD) and they are often sold either as ‘legal’ alternatives to this drug or misleadingly sold as LSD itself. NBOMe compounds are sold as freebase, hydrochlorides or can be complexed to hydroxypropyl beta-cyclodextrin (HPBCD) to increase bioavailability. Like LSD, NBOMe compounds are active at very low doses and therefore are often sold in the form of paper blotters which are administered by placing under the tongue.
Some of the NBOMe compounds most commonly encountered by law enforcement agencies include 25D-NBOMe-2-(2,5-Dimethoxy-4-methylphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (see FIG. 1A, 1B), 25B-NBOMe-2-(4-Bromo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (see FIG. 1A, 1B), 25I-NBOMe-2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl] ethanamine (see FIG. 1 1A, 1B), 25C-NBOMe-2-(4-Chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (see FIG. 1A, 1B) and 25H-NBOMe-2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (see FIG. 1A, 1B).
The exact pharmacological and toxicological effects of many of these synthetic compounds in humans are unknown and can be unpredictable. The onset of effects is rapid and the duration is generally 2-4 hours but they can last much longer depending of the dose. Side effects may last up to 7 days however there are some reports of side effects persisting for months after use. Clinical features recorded in a case study of 25I-NBOMe use included tachycardia, hypertension, agitation, aggression, visual and auditory hallucinations, seizures, hyperplexia, clonus, elevated white cell count, elevated creatine kinase, metabolic acidosis and acute kidney injury (Hill et al 2013). NBOMe compounds have been associated with a number of deaths.
Many governments around the world have taken steps to illegalise this NBOMe family of novel designer drugs. For example, the UK home office issued a temporary class drug order (TCDO) on 4 Jun. 2013, which took effect on 10 Jun. 2013, prohibiting the production, import and sale of NBOMe compounds. Subsequently all N-Benzyl phenethylamines have been placed on the permanent controlled list and will be class A drugs in the UK from 10 Jun. 2014. Similarly in the United States the DEA made 25B-NBOMe, 25I-NBOMe and 25C-NBOMe schedule I controlled drugs for at least 2 years from 15 Nov. 2013.
Current analytical methods use mass-spectrometry (MS) in conjunction with gas chromatography (GC) or liquid chromatography (LC) (e.g. Poklis et al 2014). A disadvantage of such methods of detection is that they require expensive equipment and highly trained staff. On the other hand, immunoassays are known in the art as relatively cost effective, simplistic and rapid alternatives to MS based analysis. There remains a need for an assay which is not only sensitive to the NBOMe compounds currently found in seized drugs, but that can also detect analogues and derivatives which may make their way onto the market in future so as to enable improvements in the forensic toxicological and clinical analysis of the intake of these ever evolving designer drugs.